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1
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Corradi C, Gentiluomo M, Adsay V, Sainz J, Camisa PR, Wlodarczyk B, Crippa S, Tavano F, Capurso G, Campa D. Multi-omic markers of intraductal papillary mucinous neoplasms progression into pancreatic cancer. Semin Cancer Biol 2025; 109:25-43. [PMID: 39733817 DOI: 10.1016/j.semcancer.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 12/31/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery. One viable strategy to reduce PDAC death burden associated with the disease is to focus on precursor lesions and identify markers able to predict who will evolve into PDAC. While most PDACs are believed to be preceded by pancreatic intraepithelial neoplasms (PanINs), 5-10 % arise from Intraductal papillary mucinous neoplasms (IPMNs), which are mass-forming cystic lesions that are very common in the general population. IPMNs offer an invaluable model of pancreatic carcinogenesis for researchers to analyse, as well as a target population for PDAC early detection by clinicians. The evolution of IPMN into cancer is a complex and multistep process, therefore the identification of individual markers will not be the solution. In recent years, multiple omics technologies have been instrumental to identify possible biomarkers of IPMN progression and carcinogenesis. The only foreseeable strategy will be to integrate multi-omics data, alongside clinical and morphological features, into a progression score or signature using either standard epidemiologic tools or artificial intelligence. The aim of this manuscript is to review the current knowledge on genetic biomarkers and to briefly mention also additional omics, such as metabolomics, the exposome, the miRNome and epigenomics of IPMNs.
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Affiliation(s)
| | | | - Volkan Adsay
- Department of Pathology, Koç University School of Medicine and Koç University Research Center for Translational Medicine, Istanbul, Turkey
| | - Juan Sainz
- Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain
| | - Paolo Riccardo Camisa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Barbara Wlodarczyk
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Stefano Crippa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Tavano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Gabriele Capurso
- Vita-Salute San Raffaele University, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy.
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Tharrun Daniel Paul L, Munuswamy-Ramanujam G, Kumar RCS, Ramachandran V, Gnanasampanthapandian D, Palaniyandi K. Recent advancement in molecular markers of pancreatic cancer. BIOMARKERS IN CANCER DETECTION AND MONITORING OF THERAPEUTICS 2024:121-149. [DOI: 10.1016/b978-0-323-95114-2.00025-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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3
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Teske C, Weitz J, Meier F, Kühn JP, Riediger C. Lymphoepithelial cyst mimicking malignant pancreatic signs: a case report. J Med Case Rep 2023; 17:359. [PMID: 37599365 PMCID: PMC10440886 DOI: 10.1186/s13256-023-04087-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 07/18/2023] [Indexed: 08/22/2023] Open
Abstract
BACKGROUND A lymphoepithelial cyst of the pancreas is a rare benign lesion that is difficult to diagnose preoperatively and challenging in distinguishing from potentially malignant cystic pancreatic neoplasms. A diagnostic step-up approach is recommended to clarify the lesion's dignity and specify a treatment plan. CASE PRESENTATION Here, we describe a case of a 51-year-old male European with a lymphoepithelial cyst of the pancreas mimicking malignant features in a mid-age male patient with abdominal pain and unintended weight loss. CONCLUSION Patients with indeterminate cystic pancreatic lesions should be examined by a multidisciplinary diagnostic team in a step-up approach to clarify the lesion's entity. In the case of incidentally found lymphoepithelial cysts of the pancreas, a watchful waiting strategy might be clinically reasonable if the diagnosis is proven.
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Affiliation(s)
- Christian Teske
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
- German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
- Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
| | - Frieder Meier
- Department of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Jens-Peter Kühn
- Department of Radiology, Institute of Diagnostic and Interventional Radiology, University Hospital Carl Gustav Carus, TU, Dresden, Germany
| | - Carina Riediger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
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4
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Rogowska JO, Durko Ł, Malecka-Wojciesko E. The Latest Advancements in Diagnostic Role of Endosonography of Pancreatic Lesions. J Clin Med 2023; 12:4630. [PMID: 37510744 PMCID: PMC10380545 DOI: 10.3390/jcm12144630] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/29/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
Endosonography, a minimally invasive imaging technique, has revolutionized the diagnosis and management of pancreatic diseases. This comprehensive review highlights the latest advancements in endosonography of the pancreas, focusing on key technological developments, procedural techniques, clinical applications and additional techniques, which include real-time elastography endoscopic ultrasound, contrast-enhanced-EUS, EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. EUS is well established for T-staging and N-staging of pancreaticobiliary malignancies, for pancreatic cyst discovery, for identifying subepithelial lesions (SEL), for differentiation of benign pancreaticobiliary disorders or for acquisition of tissue by EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. This review briefly describes principles and application of EUS and its related techniques.
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Affiliation(s)
| | - Łukasz Durko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-647 Lodz, Poland
| | - Ewa Malecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-647 Lodz, Poland
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5
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Maeda C, Ono Y, Hayashi A, Takahashi K, Taniue K, Kakisaka R, Mori M, Ishii T, Sato H, Okada T, Kawabata H, Goto T, Tamamura N, Omori Y, Takahashi K, Katanuma A, Karasaki H, Liss AS, Mizukami Y. Multiplex Digital PCR Assay to Detect Multiple KRAS and GNAS Mutations Associated with Pancreatic Carcinogenesis from Minimal Specimen Amounts. J Mol Diagn 2023; 25:367-377. [PMID: 36965665 DOI: 10.1016/j.jmoldx.2023.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 02/14/2023] [Accepted: 02/24/2023] [Indexed: 03/27/2023] Open
Abstract
Digital PCR (dPCR) allows for highly sensitive quantification of low-frequency mutations and facilitates early detection of cancer. However, low-throughput targeting of single hotspots in dPCR hinders variant specification when multiple probes are used. We developed a dPCR method to simultaneously identify major variants related to pancreatic carcinogenesis. Using a two-dimensional plot of droplet fluorescence under the optimized concentration of two fluorescent probe pools, the absolute quantification of different KRAS and GNAS variants was determined. Successful detection of the multiple driver mutations was verified in 24 surgically resected tumor samples from 19 patients and 22 fine-needle aspiration samples from patients with pancreatic ductal adenocarcinoma. Precise quantification of the variant allele frequency was optimized by using template DNA at a concentration as low as 1 to 10 ng. Furthermore, amplicons targeting multiple hotspots were successfully enriched with fewer false-positive findings using high-fidelity polymerase, allowing for the detection of various KRAS and GNAS mutations with high probability in small amount of cell/tissue specimens. Using this target enrichment, mutations at a rate of 90% in small residual tissues, such as the fine-needle aspiration needle flush and microscopic lesions in resected specimens, were successfully identified. The proposed method allows for low-cost, accurate detection of driver mutations to diagnose cancers, even with minimal tissue collection.
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Affiliation(s)
- Chiho Maeda
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
| | - Yusuke Ono
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan; Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
| | - Akihiro Hayashi
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Kenji Takahashi
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Kenzui Taniue
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan; Isotope Science Center, The University of Tokyo, Tokyo, Japan
| | - Rika Kakisaka
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
| | - Miyuki Mori
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
| | - Takahiro Ishii
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
| | - Hiroki Sato
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan; Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Tetsuhiro Okada
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Hidemasa Kawabata
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Takuma Goto
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Nobue Tamamura
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Yuko Omori
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan; Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Akio Katanuma
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Hidenori Karasaki
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
| | - Andrew Scott Liss
- Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Yusuke Mizukami
- Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan; Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
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6
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Okasha HH, Awad A, El-meligui A, Ezzat R, Aboubakr A, AbouElenin S, El-Husseiny R, Alzamzamy A. Cystic pancreatic lesions, the endless dilemma. World J Gastroenterol 2021; 27:2664-2680. [PMID: 34135548 PMCID: PMC8173383 DOI: 10.3748/wjg.v27.i21.2664] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/14/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
Cystic pancreatic lesions involve a wide variety of pathological entities that include neoplastic and non-neoplastic lesions. The proper diagnosis, differentiation, and staging of these cystic lesions are considered a crucial issue in planning further management. There are great challenges for their diagnostic models. In our time, new emerging methods for this diagnosis have been discovered. Endoscopic ultrasonography-guided fine-needle aspiration cytology with chemical and molecular analysis of cyst fluid and EUS-guided fine needle-based confocal laser endomicroscopy, through the needle microforceps biopsy, and single-operator cholangioscopy/pancreatoscopy are promising methods that have been used in the diagnosis of cystic pancreatic lesions. Hereby we discuss the diagnosis of cystic pancreatic lesions and the benefits of various diagnostic models.
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Affiliation(s)
- Hussein Hassan Okasha
- Department of Internal Medicine and Gastroenterology, Hepatology Unit, Kasr Al-Aini Hospitals, Cairo University, Cairo 11562, Egypt
| | - Abeer Awad
- Department of Internal Medicine and Gastroenterology, Hepatology Unit, Kasr Al-Aini Hospitals, Cairo University, Cairo 11562, Egypt
| | - Ahmed El-meligui
- Department of Internal Medicine and Gastroenterology, Hepatology Unit, Kasr Al-Aini Hospitals, Cairo University, Cairo 11562, Egypt
| | - Reem Ezzat
- Department of Internal Medicine and Gastroenterology, Hepatology Unit, Assuit University, Assuit 71515, Egypt
| | - Ashraf Aboubakr
- Department of Gastroenterology and Hepatology, Maadi Armed Forces Medical Complex, Military Medical Academy, Cairo 11441, Egypt
| | - Sameh AbouElenin
- Department of Gastroenterology and Hepatology, Military Medical Academy, Cairo 11441, Egypt
| | - Ramy El-Husseiny
- Department of Hepatology and Tropical Medicine, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo 11441, Egypt
| | - Ahmed Alzamzamy
- Department of Gastroenterology and Hepatology, Maadi Armed Forces Medical Complex, Military Medical Academy, Cairo 11441, Egypt
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7
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Geramizadeh B, Marzban M, Shojazadeh A, Kadivar A, Maleki Z. Intraductal papillary mucinous neoplasm of the pancreas: Cytomorphology, imaging, molecular profile, and prognosis. Cytopathology 2021; 32:397-406. [PMID: 33792980 DOI: 10.1111/cyt.12973] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 02/15/2021] [Accepted: 02/24/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) constitutes up to 20% of all pancreatic resections, and has been increasing in recent years. Histomorphological findings of IPMN are well established; however, there are not many published papers regarding the cytological findings of IPMN on fine needle aspiration (FNA) specimens. We review the cytomorphological features, molecular profile, imaging findings, and prognosis of IPMN. METHODS The English literature was thoroughly searched with key phrases containing IPMN. OBSERVATIONS IPMN is a rare entity, affecting men and women equally and is usually diagnosed at the age of 60-70 years. The characteristic imaging features include a cystic lesion with associated dilatation of the main or branch pancreatic duct, and atrophy of surrounding pancreatic parenchyma. Cytomorphological features of IPMN include papillary fragments of mucinous epithelium in a background of abundant thick extracellular mucin, a hallmark feature. IPMNs should be evaluated for high-grade dysplasia, which manifests with nuclear atypia, nuclear moulding, prominent nucleoli, nuclear irregularity, and cellular crowding. Molecular profiling of IPMN along with carcinoembryonic antigen and amylase levels is useful in predicting malignancy or high-grade dysplasia arising in IPMN. Overall, the prognosis of IPMN is excellent except in those cases with high-grade dysplasia and malignant transformation. Postoperative surveillance is required for resected IPMNs. CONCLUSION IPMN requires a multidisciplinary approach for management. Cytomorphological findings of IPMN on FNA, in conjunction with tumour markers in pancreatic fluid cytology and imaging findings, are of paramount importance in clinical decision-making for IPMN.
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Affiliation(s)
- Bita Geramizadeh
- Department of Pathology, Medical School of Shiraz University, Shiraz University of Medical Sciences, Shiraz, Iran.,Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahsa Marzban
- University of British Columbia, Vancouver, BC, Canada
| | - Alireza Shojazadeh
- Department of Pathology, Medical School of Shiraz University, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ana Kadivar
- University of Maryland, College Park, MD, USA
| | - Zahra Maleki
- Division of Cytopathology, Department of Pathology, The Johns-Hopkins Hospital, Baltimore, MD, USA
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8
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Litchinko A, Kobayashi K, Halkic N. A retrospective study of histological outcome for IPMN after surgery in Lausanne, Switzerland: A case series. Ann Med Surg (Lond) 2020; 60:110-114. [PMID: 33145018 PMCID: PMC7593259 DOI: 10.1016/j.amsu.2020.10.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 10/11/2020] [Accepted: 10/11/2020] [Indexed: 12/28/2022] Open
Abstract
Introduction Intraductal papillary mucinous neoplasm (IPMN) is a 21st century concept and its management is still controversial. Strong guidelines suggest that surgery is the safest way to prevent malignant evolution. Though the risk of neoplasia is still debated, high-morbidity and mortality surgery must be proposed for high-risk patients to prevent malignant and most likely fatal pancreatic neoplasia. Methods The aim of this study was to analyze histological results of patients who underwent operation for IPMN under the Sendai and Fukuoka guidelines. From January 2005 to August 2016, 491 consecutive patients who underwent pancreatic resection in Lausanne University Hospital were analyzed, including 18 IPMN with surgical indication according to the Sendai and Fukuoka criteria. Results Thirteen (68.4%) patients had benign histopathology after surgery (the non-malignant group). Of the patients with malignant pathology, four (21%) had high-grade dysplasia and two (20.1%) had invasive carcinoma (the malignant group). The median patient age (p = 0.011) and preoperative Carbohydrate Antigen 19–9 (CA19-9) (p = 0.030) were significantly higher in the malignant group than in the non-malignant group. Discussion The use of the current criteria is adequate, but it may be resulting in surgery on excessive numbers of patients with IPMN. A modern decision-making strategy should be based on clinical features, precise imaging data, and biological markers.
IPMNs are pre-cancerous tumors with a potential evolution to malignant neoplasm. Revised guidelines can lead to surgical decision but with high morbidity and mortality linked to pancreatic surgery. Moderns biological markers can help to adjust surgical criteria, added to clinical and imaging features. More specific criteria are needed prior to resection, and could lead to more and more conservative management.
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Affiliation(s)
- Alexis Litchinko
- Department of Surgery, Division of Visceral Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Kosuke Kobayashi
- Department of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Nermin Halkic
- Department of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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9
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Scholten L, Latenstein AE, Aalfs CM, Bruno MJ, Busch OR, Bonsing BA, Koerkamp BG, Molenaar IQ, Ubbink DT, van Hooft JE, Fockens P, Glas J, DeVries JH, Besselink MG. Prophylactic total pancreatectomy in individuals at high risk of pancreatic ductal adenocarcinoma (PROPAN): systematic review and shared decision-making programme using decision tables. United European Gastroenterol J 2020; 8:865-877. [PMID: 32703081 PMCID: PMC7707864 DOI: 10.1177/2050640620945534] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background Individuals with a very high lifetime risk of developing pancreatic ductal adenocarcinoma; for example, hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm, may wish to discuss prophylactic total pancreatectomy but strategies to do so are lacking. Objective To develop a shared decision-making programme for prophylactic total pancreatectomy using decision tables. Methods Focus group meetings with patients were used to identify relevant questions. Systematic reviews were performed to answer these questions. Results The first tables included hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm. No studies focused on prophylactic total pancreatectomy in these groups. In 52 studies (3570 patients), major morbidity after total pancreatectomy was 25% and 30-day mortality was 6%. After minimally invasive total pancreatectomy (seven studies, 35 patients) this was, respectively, 13% and 0%. Exocrine insufficiency-related symptoms occurred in 33%. Quality of life after total pancreatectomy was slightly lower compared with the general population. Conclusion The decision tables can be helpful for discussing prophylactic total pancreatectomy with individuals at high risk of pancreatic ductal adenocarcinoma.
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Affiliation(s)
- Lianne Scholten
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands.,Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Cora M Aalfs
- Department of Clinical Genetics, University of Amsterdam, Amsterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, St Antonius Hospital Nieuwegein and University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Dirk T Ubbink
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, University of Amsterdam, The Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, University of Amsterdam, The Netherlands
| | - Jolanda Glas
- Dutch Pancreatic Cancer Patient Organisation, 'Living with Hope', Utrecht, The Netherlands
| | - J Hans DeVries
- Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
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10
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Molecular Diagnosis of Cystic Neoplasms of the Pancreas: a Review. J Gastrointest Surg 2020; 24:1201-1214. [PMID: 32128679 DOI: 10.1007/s11605-020-04537-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 01/29/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prevalence of incidental pancreatic cystic neoplasms (PCNs) has increased dramatically with advancements in cross-sectional imaging. Diagnostic imaging is limited in differentiating between benign and malignant PCNs. The aim of this review is to provide an overview of biomarkers that can be used to distinguish PCNs. METHODS A review of the literature on molecular diagnosis of cystic neoplasms of the pancreas was performed. RESULTS Pancreatic cysts can be categorized into inflammatory and non-inflammatory lesions. Inflammatory cysts include pancreatic pseudocysts. Noninflammatory lesions include both mucinous and non-mucinous lesions. Mucinous lesions include intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm. Non-mucinous lesions include serous cystadenoma and solid-pseudopapillary tumor of the pancreas. Imaging, cyst aspiration, and histologic findings, as well as carcinoembryonic antigen and amylase are commonly used to distinguish between cyst types. However, molecular techniques to detect differences in genetic mutations, protein expression, glycoproteomics, and metabolomic profiling are important developments in distinguishing between cyst types. DISCUSSION Nomograms incorporating common clinical, laboratory, and imaging findings have been developed in a better effort to predict malignant IPMN. The incorporation of top molecular biomarker candidates to nomograms may improve the predictive ability of current models to more accurately diagnose malignant PCNs.
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11
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Hao S, Takahashi C, Snyder RA, Parikh AA. Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future. Int J Mol Sci 2020; 21:ijms21031147. [PMID: 32050465 PMCID: PMC7037360 DOI: 10.3390/ijms21031147] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/04/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022] Open
Abstract
A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing.
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Affiliation(s)
- Scarlett Hao
- Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; (S.H.); (C.T.)
| | - Caitlin Takahashi
- Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; (S.H.); (C.T.)
| | - Rebecca A. Snyder
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA;
| | - Alexander A. Parikh
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA;
- Correspondence: ; Tel.: +1-252-744-4110
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12
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Iwashita T, Uemura S, Mita N, Iwasa Y, Ichikawa H, Senju A, Yasuda I, Shimizu M. Utility of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and management of pancreatic cystic lesions: Differences between the guidelines. Dig Endosc 2020; 32:251-262. [PMID: 31709639 DOI: 10.1111/den.13579] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 10/29/2019] [Accepted: 11/07/2019] [Indexed: 12/18/2022]
Abstract
Recent advances and frequent use of cross-sectional imaging studies have increased opportunities for incidental diagnoses of pancreatic cystic lesions (PCL). In the management of PCL, distinguishing between mucinous versus non-mucinous and malignant versus benign cysts is important to diagnose pancreatic cancer in its early stage. For this reason, there have been several guidelines to manage PCL. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) play important roles in the guidelines, although there are some differences in their roles. In this review, we aimed to evaluate the current status of EUS and EUS-FNA in the management of PCL and the status of these procedures in the guidelines.
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Affiliation(s)
- Takuji Iwashita
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Shinya Uemura
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Naoki Mita
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Yuhei Iwasa
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Hironao Ichikawa
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Akihiko Senju
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Ichiro Yasuda
- Third Department of Internal Medicine, University of Toyama Hospital, Toyama, Japan
| | - Masahito Shimizu
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
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13
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Tanaka M, Heckler M, Liu B, Heger U, Hackert T, Michalski CW. Cytologic Analysis of Pancreatic Juice Increases Specificity of Detection of Malignant IPMN-A Systematic Review. Clin Gastroenterol Hepatol 2019; 17:2199-2211.e21. [PMID: 30630102 DOI: 10.1016/j.cgh.2018.12.034] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 12/25/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can progress to cancer. Biomarkers have been identified that were reported to increase the accuracy of identification of malignant lesions; we performed a systematic review of the accuracy of these markers. METHODS We performed a systematic review of published studies on biomarkers of malignant IPMNs by searching MEDLINE and Web of Science databases from January 2005 through December 2017. Our methods were developed based on the Meta-analysis Of Observational Studies in Epidemiology guidelines. Pooled sensitivity, specificity, receiver operating characteristic curves, and their respective areas under the curve (AUC) were calculated from groups of markers (cell-, protein-, or DNA-based) measured in samples collected before and after surgery. A hypothetical test model was developed to determine how to meaningfully amend the revised Fukuoka guidelines, focusing on increasing test specificity for patients with IPMNs that have worrisome features. RESULTS We collected data from 193 published studies, comprising 12,297 patients, that analyzed 7 preoperative and 21 postoperative markers of IPMNs. The 3 biomarkers that identified malignant IPMNs with the largest AUC values were pancreatic juice cytology (AUC, 0.84; sensitivity, 0.54; specificity, 0.91), serum protein carbohydrate antigen 19-9 (AUC, 0.81; sensitivity, 0.45; specificity, 0.90), and cyst fluid cytology (AUC, 0.82; sensitivity, 0.57; specificity, 0.84). A combination of cytologic and immunohistochemical analysis of MUC1 and MUC2 in pancreatic juice samples identified malignant IPMNs with the largest AUC and sensitivity values (AUC, 0.85; sensitivity, 0.85; specificity, 0.65). In a test model, inclusion of cytologic analysis of pancreatic juice in the guideline algorithm significantly increased the specificity of detection of malignant IPMNs. CONCLUSIONS In a systematic review, we found cytologic analysis of pancreatic juice to have the greatest effect in increasing the specificity of detection of malignant IPMNs. We propose addition of this test to the Fukuoka guidelines for assessment of patients with IPMNs with worrisome features.
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Affiliation(s)
- Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Max Heckler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Bing Liu
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Ulrike Heger
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany.
| | - Christoph W Michalski
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany; Department of Surgery, Halle University Hospital, Martin Luther University Halle-Wittenberg, Halle, Germany
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14
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Lim J, Allen PJ. The diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas: has progress been made? Updates Surg 2019; 71:209-216. [PMID: 31175628 DOI: 10.1007/s13304-019-00661-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Abstract
Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are premalignant mucin-producing epithelial tumors that arise from the pancreatic ductal system. These cystic tumors represent 15-30% of cystic lesions of the pancreas [Basturk et al. in Am J Surg Pathol 39(12):1730-1741, 1; Ferrone et al. in Arch Surg (Chicago, Ill: 1960) 144(5):448-454, 2, Kosmahl et al. in Virchows Arch Int J Pathol 445(2):168-178, 3; Spinelli et al. in Ann Surg. 239(5):651-657, 4]. It is believed that IPMN can progress from low-grade dysplasia to high-grade dysplasia to invasive cancer, and this pathway of progression accounts for 20-30% of pancreatic cancer [Adsay et al. in Am J Surg Pathol 28(7):839-848, 5; Tanaka et al. in J Gastroenterol 40(7):669-675, 6; Wu et al. in Sci Transl Med 3(92):92ra66, 7]. Furthermore, it is also widely believed that IPMN represent a field defect of the pancreas in which the entire ductal system is at risk of developing invasive carcinoma, not only in the area of radiographically detectable IPMN, and thus the remaining gland should undergo surveillance after partial pancreatectomy [Salvia et al. in Ann Surg 239(5):678-685, 8; Izawa et al. in Cancer 92(7):1807-1817, 9; Yamaguchi and Tanaka in Jpn J Clin Oncol 41(7):836-840, 10]. Increasingly, surgeons are faced with the dilemma between recommending highly complex resections-that have significant morbidity and mortality-in patients who may have low-risk IPMN (low-grade dysplasia), or alternatively, recommending observation for those who could possibly be harboring a radiographically occult malignancy. Given the complexity of the management decisions for patients with IPMN, the purpose of this paper is to review the current literature and to provide a summary of how accurate we are currently with the identification of high-grade dysplasia or progression to carcinoma in patients who present with IPMN.
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Affiliation(s)
- Jenny Lim
- Department of Surgical Oncology, Duke University, Durham, NC, 27710, USA.
| | - Peter J Allen
- Department of Surgical Oncology, Duke University, Durham, NC, 27710, USA
- Duke Cancer Institute, Duke Health System, Durham, NC, 27710, USA
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15
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Kamata K, Kitano M. Endoscopic diagnosis of cystic lesions of the pancreas. Dig Endosc 2019; 31:5-15. [PMID: 30085364 DOI: 10.1111/den.13257] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 08/02/2018] [Indexed: 12/13/2022]
Abstract
Endoscopic methods are increasingly used in the diagnosis of cystic lesions of the pancreas. The two major endoscopic approaches are endoscopic ultrasonography (EUS) and transpapillary diagnosis. EUS-guided fine-needle aspiration cytology and EUS-guided fine needle-based confocal laser endomicroscopy have been used in the differential diagnosis of mucinous and non-mucinous pancreatic cysts. EUS is the most sensitive modality for detecting mural nodules (MN) in intraductal papillary mucinous neoplasms (IPMN). Contrast-enhanced harmonic EUS (CH-EUS), as an add-on to EUS, is useful for identifying and characterizing MN. Recent studies show that CH-EUS has a sensitivity of 60-100% and a specificity of 75-92.9% for diagnosing malignant cysts. Intraductal ultrasonography and peroral pancreatoscopy are especially useful for detecting MN and IPMN. A recent meta-analysis showed that cytological assessment of pancreatic juice using a transpapillary approach had a pooled sensitivity, specificity, and accuracy of 35.1%, 97.2%, and 92.9%, respectively, for diagnosing malignant IPMN. Further studies are warranted to determine the indications for each of these novel techniques in assessing cystic lesions of the pancreas.
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Affiliation(s)
- Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
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16
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Volckmar AL, Endris V, Gaida MM, Leichsenring J, Stögbauer F, Allgäuer M, von Winterfeld M, Penzel R, Kirchner M, Brandt R, Neumann O, Sültmann H, Schirmacher P, Rudi J, Schmitz D, Stenzinger A. Next generation sequencing of the cellular and liquid fraction of pancreatic cyst fluid supports discrimination of IPMN from pseudocysts and reveals cases with multiple mutated driver clones: First findings from the prospective ZYSTEUS biomarker study. Genes Chromosomes Cancer 2018; 58:3-11. [PMID: 30230086 DOI: 10.1002/gcc.22682] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 09/07/2018] [Accepted: 09/10/2018] [Indexed: 12/15/2022] Open
Abstract
Approximately half of all pancreatic cysts are neoplastic, mainly comprising intraductal papillary mucinous neoplasms (IPMN), which can progress to invasive carcinoma. Current Fukuoka guidelines have limited sensitivity and specificity in predicting progression of asymptomatic pancreatic cysts. We present first results of the prospective ZYSTEUS biomarker study investigating (i) whether detection of driver mutations in IPMN by liquid biopsy is technically feasible, (ii) which compartment of IPMN is most suitable for analysis, and (iii) implications for clinical diagnostics. Twenty-two patients with clinical inclusion criteria were enrolled in ZYSTEUS. Fifteen cases underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration and cytological diagnostics. Cellular and liquid fraction of the cysts of each case were separated and subjected to deep targeted next generation sequencing (NGS). Clinical parameters, imaging findings (EUS and MRI), and follow-up data were collected continuously. All IPMN cases (n = 12) showed at least one mutation in either KRAS (n = 11) or GNAS (n = 4). Three cases showed both KRAS and GNAS mutations. Six cases harbored multiple KRAS/GNAS mutations. In the three cases with pseudocysts, no KRAS or GNAS mutations were detected. DNA yields were higher and showed higher mutation diversity in the cellular fraction. In conclusion, mutation detection in pancreatic cyst fluid is technically feasible with more robust results in the cellular than in the liquid fraction. Current results suggest that, together with imaging, targeted sequencing supports discrimination of IPMN from pseudocysts. The prospective design of ZYSTEUS will provide insight into diagnostic value of NGS in preoperative risk stratification. Our data provide evidence for an oligoclonal nature of IPMN.
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Affiliation(s)
- Anna-Lena Volckmar
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Volker Endris
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Matthias M Gaida
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Jonas Leichsenring
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Fabian Stögbauer
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Michael Allgäuer
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | | | - Roland Penzel
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Martina Kirchner
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Regine Brandt
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Olaf Neumann
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Holger Sültmann
- Division of Cancer Genome Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Peter Schirmacher
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Jochen Rudi
- Department of Gastroenterology, Oncology and Diabetology, Theresienkrankenhaus und St. Hedwigsklinik, Academic Teaching Hospital, Mannheim, Germany
| | - Daniel Schmitz
- Department of Gastroenterology, Oncology and Diabetology, Theresienkrankenhaus und St. Hedwigsklinik, Academic Teaching Hospital, Mannheim, Germany
| | - Albrecht Stenzinger
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.,German Cancer Consortium (DKTK), Partner Site Heidelberg, and German Cancer Research Center (DKFZ), Heidelberg, Germany
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17
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Kaplan JH, Gonda TA. The Use of Biomarkers in the Risk Stratification of Cystic Neoplasms. Gastrointest Endosc Clin N Am 2018; 28:549-568. [PMID: 30241643 DOI: 10.1016/j.giec.2018.05.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Cyst fluid biomarkers may be used to identify pancreatic cyst subtypes. Biomarkers are selected based on their ability to accurately distinguish mucinous from nonmucinous cysts and to risk stratify cysts based on malignant potential. Biomarkers of interest include but are not limited to amylase, oncogenes, DNA analysis, and epigenetic markers. The introduction of next-generation sequencing and molecular panels has aided in improved diagnostic accuracy and risk stratification. This review presents the diagnostic performance of currently available biomarkers and proposes an algorithm to incorporate their use in the diagnosis of pancreatic cysts.
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Affiliation(s)
- Jeremy H Kaplan
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, 161 Fort Washington Avenue, New York, NY 10032, USA
| | - Tamas A Gonda
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, 161 Fort Washington Avenue, New York, NY 10032, USA.
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18
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Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics. Cancers (Basel) 2018; 10:cancers10060174. [PMID: 29865155 PMCID: PMC6025626 DOI: 10.3390/cancers10060174] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 05/29/2018] [Accepted: 05/30/2018] [Indexed: 12/18/2022] Open
Abstract
For patients with metastatic pancreatic cancer that are not eligible for surgery, signal-targeted therapies have so far failed to significantly improve survival. These therapeutic options have been tested in phase II/III clinical trials mostly in combination with the reference treatment gemcitabine. Innovative therapies aim to annihilate oncogenic dependency, or to normalize the tumoural stroma to allow immune cells to function and/or re-vascularisation to occur. Large scale transcriptomic and genomic analysis revealed that pancreatic cancers display great heterogeneity but failed to clearly delineate specific oncogene dependency, besides oncogenic Kras. Beyond these approaches, proteomics appears to be an appropriate approach to classify signal dependency and to identify specific alterations at the targetable level. However, due to difficulties in sampling, proteomic data for this pathology are scarce. In this review, we will discuss the current state of clinical trials for targeted therapies against pancreatic cancer. We will then highlight the most recent proteomic data for pancreatic tumours and their metastasis, which could help to identify major oncogenic signalling dependencies, as well as provide future leads to explain why pancreatic tumours are intrinsically resistant to signal-targeted therapies. We will finally discuss how studies on phosphatidylinositol-3-kinase (PI3K) signalling, as the paradigmatic pro-tumoural signal downstream of oncogenic Kras in pancreatic cancer, would benefit from exploratory proteomics to increase the efficiency of targeted therapies.
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19
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Yadav DK, Bai X, Yadav RK, Singh A, Li G, Ma T, Chen W, Liang T. Liquid biopsy in pancreatic cancer: the beginning of a new era. Oncotarget 2018; 9:26900-26933. [PMID: 29928492 PMCID: PMC6003564 DOI: 10.18632/oncotarget.24809] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 02/25/2018] [Indexed: 12/21/2022] Open
Abstract
With dismal survival rate pancreatic cancer remains one of the most aggressive and devastating malignancy. Predominantly, due to the absence of a dependable methodology for early identification and limited therapeutic options for advanced disease. However, it takes over 17 years to develop pancreatic cancer from initiation of mutation to metastatic cancer; therefore, if diagnosed early; it may increase overall survival dramatically, thus, providing a window of opportunity for early detection. Recently, genomic expression analysis defined 4 subtypes of pancreatic cancer based on mutated genes. Hence, we need simple and standard, minimally invasive test that can monitor those altered genes or their associated pathways in time for the success of precision medicine, and liquid biopsy seems to be one answer to all these questions. Again, liquid biopsy has an ability to pair with genomic tests. Additionally, liquid biopsy based development of circulating tumor cells derived xenografts, 3D organoids system, real-time monitoring of genetic mutations by circulating tumor DNA and exosome as the targeted drug delivery vehicle holds lots of potential for the treatment and cure of pancreatic cancer. At present, diagnosis of pancreatic cancer is frantically done on the premise of CA19-9 and radiological features only, which doesn't give a picture of genetic mutations and epigenetic alteration involved. In this manner, the current diagnostic paradigm for pancreatic cancer diagnosis experiences low diagnostic accuracy. This review article discusses the current state of liquid biopsy in pancreatic cancer as diagnostic and therapeutic tools and future perspectives of research in the light of circulating tumor cells, circulating tumor DNA and exosomes.
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Affiliation(s)
- Dipesh Kumar Yadav
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Rajesh Kumar Yadav
- Department of Pharmacology, Gandaki Medical College, Tribhuwan University, Institute of Medicine, Pokhara 33700, Nepal
| | - Alina Singh
- Department of Surgery, Bir Hospital, National Academy of Medical Science, Kanti Path, Kathmandu 44600, Nepal
| | - Guogang Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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20
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Duconseil P, Adham M, Sauvanet A, Autret A, Périnel J, Chiche L, Mabrut JY, Tuech JJ, Mariette C, Turrini O. Fukuoka-Negative Branch-Duct IPMNs: When to Worry? A Study from the French Surgical Association (AFC). Ann Surg Oncol 2018; 25:1017-1025. [PMID: 29392508 DOI: 10.1245/s10434-017-6318-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND This study analyzed the pathologic findings for patients with Fukuoka-negative branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) who theoretically were eligible for surveillance care with follow-up assessment, but instead underwent resection. METHODS From January 2005 to December 2012, 820 patients underwent evaluation for IPMN. At initial staging, 319 patients had BD-IPMN, and 89 of these patients presented with Fukuoka-negative criteria. These 89 patients were included in this study. RESULTS Of the 89 patients, 55 (62%) underwent pancreatectomy. After pathologic examination, the ultimate diagnosis was MT-IPMN for 20 (36%) of these patients (the MT group) and BD-IPMN for 35 (64%) of these patients (the BD group). The remaining 34 patients (38%) underwent enucleation. The patients in the MT group were more likely to be male (P = 0.01) and to have a higher rate of recent (< 1 year) diabetes mellitus diagnosis (P = 0.007) than the patients in the BD group. In the multivariate analysis, diabetes mellitus was independently associated with involvement of the main pancreatic duct (P = 0.05). Malignancy was diagnosed for 14 (16%) of the 89 patients. The rate of invasive IPMN was higher in the MT group than in the BD group (20% vs. 0%, P = 0.02). The 5-year overall survival rate was 100% for the BD group and 84% for the MT group (P = 0.02). For the male patients with diabetes mellitus, the rate of malignancy rose to 67%. CONCLUSIONS For patients with a diagnosis of Fukuoka-negative BD-IPMN, resection should be considered primarily for male patients with a recent diabetes mellitus diagnosis.
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Affiliation(s)
- Pauline Duconseil
- Department of Surgery, Hôpital Nord, Marseille, France. .,Department of Digestive Surgery, Hôpital Nord, Marseille, France.
| | - Mustapha Adham
- Department of Surgery, Hôpital Edouard-Herriot, Lyon, France
| | | | - Aurélie Autret
- Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France
| | - Julie Périnel
- Department of Surgery, Hôpital Edouard-Herriot, Lyon, France
| | - Laurence Chiche
- Department of Surgery, Maison du Haut-Lévêque, Bordeaux, France
| | | | | | | | - Olivier Turrini
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
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21
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Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas. Langenbecks Arch Surg 2017; 403:151-194. [DOI: 10.1007/s00423-017-1644-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 11/24/2017] [Indexed: 02/07/2023]
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22
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Pimienta M, Edderkaoui M, Wang R, Pandol S. The Potential for Circulating Tumor Cells in Pancreatic Cancer Management. Front Physiol 2017. [PMID: 28626429 PMCID: PMC5454071 DOI: 10.3389/fphys.2017.00381] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Pancreatic cancer is one the most lethal malignancies. Only a small proportion of patients with this disease benefit from surgery. Chemotherapy provides only a transient benefit. Though much effort has gone into finding new ways for early diagnosis and treatment, average patient survival has only been improved in the order of months. Circulating tumor cells (CTCs) are shed from primary tumors, including pre-malignant phases. These cells possess information about the genomic characteristics of their tumor source in situ, and their detection and characterization holds potential in early cancer diagnosis, prognosis, and treatment. Liquid Biopsies present an alternative to tumor biopsy that are hard to sample. Below we summarize current methods of CTC detection, the current literature on CTCs in pancreatic cancer, and future perspectives.
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Affiliation(s)
- Michael Pimienta
- University of California, San Diego School of MedicineLa Jolla, CA, United States.,Cedars-Sinai Medical Center, Basic and Translational Pancreas ResearchLos Angeles, CA, United States
| | - Mouad Edderkaoui
- Cedars-Sinai Medical Center, Basic and Translational Pancreas ResearchLos Angeles, CA, United States
| | - Ruoxiang Wang
- Cedars-Sinai Medical Center, Basic and Translational Pancreas ResearchLos Angeles, CA, United States
| | - Stephen Pandol
- Cedars-Sinai Medical Center, Basic and Translational Pancreas ResearchLos Angeles, CA, United States
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23
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Affiliation(s)
- Omer Basar
- Pancreas Biliary Center, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States ,Department of Gastroenterology, Hacettepe Medical School, Ankara, Turkey,Corresponding author Omer Basar, MD 3-H GI Associates, Zero Emerson Place, Blossom St. Massachusetts General HospitalBoston, MA, 02114+1-617-724-5997
| | - William R. Brugge
- Pancreas Biliary Center, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States
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